Table 8.
Feasibility testing of the ESMO-MCBS v1.1 for relapsed/refractory multiple myeloma (n=15)
| Medication | Trial name | Setting | Primary outcome | PFS control | PFS gain | PFS HR | OS control | OS gain | OS HR | RR (DOR) | QOL | Toxicity | ESMO-MCBS score | ESMO-MCBS form | Reference(s) |
| Dexamethasone ± lenalidomide | CC-5013- MM-010 | Relapsed/refractory | TTP | 4.7 months | 6.6 months | 0.35 (0.27– 0.46) | 20.6 months | NA | 0.66 (0.45–0.96) | 3 | 2b | 85 | |||
| Lenalidomide-d ± carfilzomib | ASPIRE | Relapsed/refractory | PFS | 17.6 months | 8.7 months | 0.69 (0.57–0.83) | 40.4 months | 7.9 months | 0.79 (0.67– 0.95) | Improved (+1 point) | Slightly increased | 4 | 2a | 86 87 | |
| Lenalidomide-d ± ixazomib | TOURMALINE-MM1 | Relapsed/refractory | PFS (interim) | 14.7 months | 5.9 months | 0.74 (0.59–0.94) | Immature | Not improved | 3 | 2b | 88 | ||||
| Lenalidomide-d ± daratumumab | POLLUX | Relapsed/refractory | PFS (interim) | 18.4 months | 16+months | 0.37 (0.27–0.52) | Immature | Higher haematological toxicities | 3 | 2b | 89 | ||||
| Lenalidomide-d ± elotuzumab | ELOQUENT-2 | Relapsed/refractory | Coprimary PFS and ORR (interim) | 14.9 months 57% at 12 months | 4.5 months 11% at 12 months | 0.70 (0.57–0.85) | 39.6 months | 8.7 months | 0.78 (0.63– 0.96) | No difference | Slightly higher SAEs | 3 | 2a | 90 91 | |
| Dexamethasone ± bortezomib | APEX | Relapsed/refractory | TTP | 3.5 months | 2.7 months | 0.55 (p=0.001) | 23.7 months | 6.1 months | 0.77 (p=0.027) | 3 | 2b | 92 93 | |||
| Carfilzomib-d versus bortezomib-d | ENDEAVOR | Relapsed/refractory | PFS | 9.4 months | 9.3 months | 0.53 (0.44–0.65) | 40 months | 7.6 months | 0.79 (0.65– 0.96) | Improved (abstract only) | Slightly higher SAEs | 3 | 2a | 94 95 | |
| Bortezomib-d ± daratumumab | CASTOR | Relapsed/refractory | PFS | 7.1 months 26.9% at 12 months | 9.6 months 33.8% at 12 months | 0.31 (0.24–0.39) | Immature | Higher haematological toxicity | 3 | 2b | 96 97 | ||||
| Bortezomib-d ±panobinostat | PANORAMA1 | Relapsed/refractory | PFS | 8.1 months | 3.9 months | 0.63 (0.52– 0.76) | 30.4 months | 3.25 months | Immature | 3% increase in PN grade ≥3 (−1 point) |
2 | 2b | 98 | ||
| Dexamethasone ± pomalidomide | MM-003 | Relapsed/refractory | PFS | 1.9 months | 2.1 months | 0.48 (0.39–0.60) | 8.1 months | 4.6 months | 0.74 (0.56– 0.97) | 4 | 2a | 99 | |||
| Pomalidomide-d ± cyclophosphamide | MMC-16705 | Relapsed/refractory ≥2 prior lines of treatment | ORR | 4.4 months | 5.1 months | NS | 64.7% vs 38.9%, gain 25.8% | 2 | 2c | 100 | |||||
| Daratumumab | SIRIUS | Relapsed/refractory | ORR | 3.7 months | 29% (7.4 months) | 2 | 3 | 101 | |||||||
| Daratumumab | GEN501 | Relapsed/refractory (16 mg/kg) | Safety | 5.6 months | 36% (NR) | 2 | 3 | 102 | |||||||
| Daratumumab +pomalidomide + d | MMY1001 | Relapsed/refractory ≥2 prior lines of treatment | Safety | 8.8 months | 17.5 months | 60% (>13 months) | 3 | 3 | 103 | ||||||
| Pomalidomide +bortezomib + d | MC1082 | Relapsed/refractory | ORR | 13.7 months | 86% | 3 | 3 | 104 |
d, dexamethasone; DOR, duration of response;ESMO-MCBS v1.1, European Society for Medical Oncology—Magnitude of Clinical Benefit Scale, version 1.1; NA, not applicable;NR, not reached; NS, not significant; ORR, overall response rate; OS, overall survival;PFS, progression-free survival; PN, polyneuropathy; QOL, quality of life; RR, response rate; SAEs, serious adverse events; TTP, time to progress.